Resistance of the renal biosynthesis of prostaglandin E2 to the inhibitory effect of indomethacin in the rat in vivo.
Our recent observation that the chronic administration of indomethacin (3.0 mg.kg-1.day) to hypertensive rats, while profoundly inhibiting the urinary excretion of 6-oxo-PGF1 alpha, dinor-6-oxo-PGF1 alpha and thromboxane B2, failed to reduce the urinary levels of PGE2, prompted us to study in more details the influence of indomethacin and of meclofenamate on the urinary excretion of prostaglandins in normal rats. A dose of 1.5 mg.kg-1 of indomethacin administered intraperitoneally was sufficient to cause a 70-75% reduction in the urinary excretion of dinor-6-oxo-PGF1 alpha and of 6-oxo-PGF1 alpha for a period of at least 12 hours. Doses of indomethacin lower than 2.5 mg.kg-1.12h beta 1 or a dose of meclofenamate equal to 5 mg.kg-1.12h beta 1 did not influence the urinary excretion of PGE2. Doses of indomethacin equal to or higher than 2.5 mg.kg-1 were needed to obtain a 50% reduction in the urinary levels of PGE2 for a period of 10-14 h. During these experiments, no circadian rhythm for the urinary excretion of 6-oxo-PGF1 alpha and of dinor-6-oxo-PGF1 alpha could be observed whereas the urine volume and the urinary excretion of PGE2 were found to be greater at night than during the day.(ABSTRACT TRUNCATED AT 250 WORDS)
Hui
R
R
Laboratory on Prostaglandins, Université de Montréal, Québec, Canada.
Falardeau
P
P
D000527:Alprostadil / Q000096:biosynthesis* / Q000652:urine; D000818:Animals; D002940:Circadian Rhythm; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D011464:Epoprostenol / Q000096:biosynthesis* / Q000652:urine; D006973:Hypertension / Q000188:drug therapy; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D008469:Meclofenamic Acid; D011464:Epoprostenol; D000527:Alprostadil; D007213:Indomethacin